U.S.-Based Trio Wins Nobel Prize for Medicine

Honored for Cracking Puzzle of How a Cell Transports Crucial Cargo Such as Hormones

A U.S.-based trio of scientists won the Nobel Prize in Physiology or Medicine for discovering the intricate machinery that transports molecules inside a cell. Gautam Naik discusses the impact of this finding on biology and medicine with cell biologist Professor Mike Cousin.

Three U.S.-based scientists shared this year's Nobel Prize in physiology or medicine for solving the enigma of how a cell transports crucial cargo—such as hormones—to the right place at the right time.

The award was given to U.S.-born James E. Rothman of Yale University and Randy W. Schekman of the University of California, Berkeley, and to Thomas C. Südhof, a German who moved to the U.S. in the 1980s and is affiliated with Stanford University.

The trio was honored for discovering "a fundamental process in cell physiology," said Juleen R. Zierath, chairman of the Nobel Committee for Physiology or Medicine, at a news conferencein Stockholm, where the award was announced.

ENLARGE

Creatures as diverse as yeast and humans share aspects of the cellular-transport mechanism that is vital to life's processes. By elucidating this mechanism, the researchers shed light on how nerve cells communicate, how pancreatic cells secrete insulin and how embryos release chemicals that spark organ development.

"The significance of the work [relates to] how cells talk to each other," said Mike Cousin, a biologist at the University of Edinburgh in Scotland. "This discovery has underpinned a lot of cell-biology research over the past 20 years."

On the practical front, the research spurred insights about how a disruption of the transport mechanism can contribute to a range of ailments, from neurological diseases and diabetes to immune disorders.

Nobel Prize Winners

For example, certain bacteria mess up the transport machinery and cause tetanus, a disease that kills thousands of newborns each year. The release of neurotransmitters is also disturbed in many cases of schizophrenia. Labs are now targeting the transport mechanism in the hope of finding treatments for such maladies.

A cell is a busy hive of a factory, making and exporting molecules in a precise, controlled way. By the 1970s, it had been established that the cell is organized into compartments, and that molecules need to move from one compartment to another and, in some cases—such as insulin—outside the cell.

It was also known that a cell's molecules are transported in membrane-bound sacs known as vesicles. But there was a central mystery about vesicles: Amid the permanently hectic traffic that occurs inside the cell, how do they know when and where to deliver their precious cargo?

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A U.S.-based trio won the Nobel Prize in Physiology or Medicine for discoveries relating to vesicle traffic, a major transport system in cells. Watch the prize announcement from Stockholm. Photo: EPA

Dr. Schekman decided to study the problem in yeast. Plenty of scientists pooh-poohed the idea, partly because they doubted that findings about a single-celled creature could ever apply to humans. They also questioned whether yeast had a robust secretion system. But Dr. Schekman persevered. By comparing normal yeast cells with genetically mutated ones in which vesicle movement was disrupted, he was able to identify genes that control the transport to different compartments and to the cell surface.

"It's not intuitive, but when you cripple the process, you gain a lot of information" about how the transportation process works, said Dr. Schekman, at a press conference in Berkeley on Monday.

That breakthrough later enabled biotechnology firms such as Genentech Inc. to exploit the secretion system in yeast. Today, genetically engineered yeast produces a large share of the world's insulin supply, which is used by diabetics. Most of the world's hepatitis B vaccine is also made in the same way.

Meanwhile, through a series of ingenious experiments, Dr. Rothman discovered specific proteins on the vesicle membrane that fuse or "dock" with matching proteins on a target membrane within the cell or on the cell's outer wall—just as if they were the two sides of a zipper. Once the docking occurs, the contents of the vesicle can be properly delivered. Because there are many such proteins that dock only in specific combinations, it ensures that the cargo gets delivered to the required location.

These steps often involve extremely precise timing and come in response to specific stimuli. This is true, for example, in the case of insulin secretion in the pancreas and in the release of brain chemicals known as neurotransmitters. But how this magic occurred was unclear—until Dr. Südhof came along.

In studying nerve cells, he discovered that when the vesicle's molecular machinery senses calcium ions, it triggers the docking process. That explains how neurotransmitters can be released from the vesicles on command.

"Without this exquisitely precise organization, the cell would lapse into chaos," the Nobel committee noted.

It's fascinating, and disturbing, how fragile intracellular messaging seems. No wonder we have so many diseases that are, essentially, messaging gone haywire (from multiple sclerosis to common auto-immune diseases). This complexity is so adaptive, but so prone to the slightest mutation or viral hijacking. Scary. Reminds me to knock a few items off my bucket list.

"If it could be demonstrated that any complex organ existed, which could not possibly have been formed by numerous, successive, slight, modifications, my theory would absolutely break down." The Origin of Species, page 154, edition 2, Oxford World's Classics.

"cracking the puzzle"? I thought puzzles were solved. No Pulitzer for the writer of the article.

But congrats to the scientists. Cells really are amazing things. There is more information in a single living cell than is contained in the all the mainframe computers in the world. We are just beginning to understand the mysteries--to learn how the machinery operates.

Fine work and wonderful results rewarded by a now questionable society. It would be outstanding if an American of wealth would establish an annual award to reward scientific and medical research success and to further such fine work.

Mr. Burish, There are facts about the awarding of the six prizes of which you are apparently unaware. Each category has its own set of persons in Sweden to evaluate and recommend to the Nobel Committee. (The Peace Prize is awarded by a Committee in Norway). The Nobel Prize in Physiology or Medicine is awarded by the Nobel Assembly at Karolinska Institutet, Stockholm. KI is a prestigious medical university. I will agree with the tone of your message regarding the 'Peace' prize, however.

The Peace Prize and the scientific prizes are handled by different groups. Not even in the same country.

The Peace Prizes for decades required that the recipient be responsible for massive slaughter and then cease it, as the qualifying factor. But for BO, a special dispensation was required, as he was clearly incapable of the magnitude of accomplishment normally required. It was awarded to enhance his self-esteem, in hope he would live up to it.

Sad to say, Ready, Fire, Aim is as ineffectual in awarding Peace Prizes as in firearms marksmanship.

You may want to complain to the Nobel Prize Committee; apparently some "moo cow type" from a low level ecole des vaches was responsible for this "insult". We wouldn't want to see Berkeley slighted, would we? :)

Since you brought it up, I wonder what's better in the long run. A prize such as the Nobel that acts as reward for achievement, or a research/charity foundation such as Bill Gates' that funds the actual research.

A prize puts scientific achievement in the limelight and encourages that way, but it feels like money directly to the research organizations would do more good.

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